白屈菜红碱逆转不同浓度葡萄糖培养的乳鼠心肌细胞肥大及其相关机制的探讨

The effect of chelerythrine on the hypertrophy of cardiac myocytes of neonatal rats induced by different glucose levels and its mechanism

研究白屈菜红碱对不同浓度葡萄糖培养的乳鼠心肌细胞肥大的作用,并进一步探讨其相关的作用机制。通过建立乳鼠心肌细胞培养模型,随机分成对照组(5mmol·L-1)、高糖组(10、15、20及25.5mmol·L-1)、高糖(25.5mmol·L-1)+不同浓度白屈菜红碱(1及8μmol·L-1)组、对照(5mmol·L?1)+不同浓度白屈菜红碱(1及8μmol·L-1)组,分别测定各组心肌细胞直径和蛋白质含量,并应用Western blotting检测心肌细胞蛋白激酶C(protein kinase C,PKC)-α、PKC-β2的表达及其磷酸化水平。结果表明,高糖培养组心肌细胞直径、蛋白质含量以及PKC-α、PKC-β2的表达和磷酸化水平均高于对照组,并呈现浓度依赖性;而分别在对照组和高糖组(25.5mmol·L-1)加入不同浓度的白屈菜红碱后,心肌细胞直径、蛋白质含量、PKC-α、PKC-β2的磷酸化水平以及PKC-α的总表达水平均降低,并且这种效应随着白屈菜红碱浓度的增高而增强;但在对照+白屈菜红碱(1μmol·L-1)组,PKC-β2的总表达水平并没有出现显著性降低。本研究表明白屈菜红碱可逆转葡萄糖诱导的乳鼠心肌细胞肥大,对高糖环境中的心肌细胞具有保护作用,其机制可能与PKC途径有关。

The purpose of this study is to investigate the effect of chelerythrine on the hypertrophy of cardiomyocytes of neonatal rats induced by different glucose levels and its mechanism. Using cultured neonatal ventricular myocytes as a model, groups were divided as： control （5 mmol·L^-1）; high glucose level （10, 15, 20, and 25.5 mmol·L^-1）; high glucose level （25.5 mmol·L^-1） add different concentrations of chelerythrine （1 and 8 mmol·L^-1）; and control glucose level （5 mmol·L^-1） add different concentrations of chelerythrine （1 and 8 mmol·L^-1）. Different groups of cardiomyocytes after adding corresponding treat factors were cultured for 48 hours. Cardiomyocytes＇ diameters and protein level were measured and the expression of PKC-α, PKC-β2, p-PKC-α, and p-PKC-β2 were measured by Western blotting. Compared with control group, neonatal myocytes cultured in high glucose levels showed increased cellular volumes, protein level and expression of PKC-α, PKC-β2, p-PKC-α, p-PKC-β2. When chelerythrine was added, cellular volumes, protein level and expression of PKC-α, PKC-β2, p-PKC-a, p-PKC-β2 were significantly reduced. But in 1 μmol·L^-1 chelerythrine group, the expression of PKC-β2 was not significantly reduced. The result suggested that chelerythrine can reverse the hypertrophy induced by different glucose levels on the cardiac myocytes, it may have protective effect against diabetic cardiomyopathy via PKC passageway.